Cerebral edema is excess accumulation of fluid (edema) in the intracellular or extracellular spaces of the brain. This typically causes impaired nerve function, increased pressure within the skull, and can eventually lead to direct compression of brain tissue and blood vessels. Symptoms vary based on the location and extent of edema and generally include headaches, nausea, vomiting, seizures, drowsiness, visual disturbances, dizziness, and in severe cases, death.
Cerebral edema is commonly seen in a variety of brain injuries including ischemic stroke, subarachnoid hemorrhage, traumatic brain injury, subdural, epidural, or intracerebral hematoma, hydrocephalus, brain cancer, brain infections, low blood sodium levels, high altitude, and acute liver failure. Diagnosis is based on symptoms and physical examination findings and confirmed by serial neuroimaging (computed tomography scans and magnetic resonance imaging).
The treatment of cerebral edema depends on the cause and includes monitoring of the person's airway and intracranial pressure, proper positioning, controlled hyperventilation, medications, fluid management, steroids. Extensive cerebral edema can also be treated surgically with a decompressive craniectomy. Cerebral edema is a major cause of brain damage and contributes significantly to the mortality of ischemic strokes and traumatic brain injuries.
As cerebral edema is present with many common cerebral pathologies, the epidemiology of the disease is not easily defined. The incidence of this disorder should be considered in terms of its potential causes and is present in most cases of traumatic brain injury, central nervous system tumors, brain ischemia, and intracerebral hemorrhage. For example, malignant brain edema was present in roughly 31% of people with ischemic strokes within 30 days after onset.
Signs and symptoms
The extent and severity of the symptoms of cerebral edema depend on the exact etiology but are generally related to an acute increase of the pressure within the skull. As the skull is a fixed and inelastic space, the accumulation of cerebral edema can displace and compress vital brain tissue, cerebral spinal fluid, and blood vessels, according to the Monro–Kellie doctrine.
Increased intracranial pressure (ICP) is a life-threatening surgical emergency marked by symptoms of headache, nausea, vomiting, decreased consciousness. Symptoms are frequently accompanied by visual disturbances such as gaze paresis, reduced vision, and dizziness. Increased pressures within the skull can cause a compensatory elevation of blood pressure to maintain cerebral blood flow, which, when associated with irregular breathing and a decreased heart rate, is called the Cushing reflex. The Cushing reflex often indicates compression of the brain on brain tissue and blood vessels, leading to decreased blood flow to the brain and eventually death.
Causes Cerebral edema is frequently encountered in acute brain injuries from a variety of origins, including but not limited to:
Traumatic brain injury Stroke Tumors Infections (such as a brain abscess or meningitis) Hepatic encephalopathy Posterior reversible encephalopathy syndrome Radiation-induced brain edema Post-surgical changes Amyloid-related imaging abnormalities associated with edema (ARIA-E) Hyponatremia High-altitude cerebral edema
Risk factors Cerebral edema is present with many common cerebral pathologies and risk factors for development of cerebral edema will depend on the cause. The following were reliable predictors for development of early cerebral edema in ischemic strokes:
Younger age Higher severity of symptoms on the National Institutes of Health Stroke Scale Signs of current ischemia on clinical exam Decreased level of consciousness Hyper dense artery sign and larger affected area on CT imaging Higher blood glucose
Classification Cerebral edema has been traditional classified into two major sub-types: cytotoxic and vasogenic cerebral edema. This simple classification helps guide medical decision making and treatment of patients affected with cerebral edema. There are, however, several more differentiated types including but not limited to interstitial, osmotic, hydrostatic, and high altitude associated edema. Within one affected person, many individual sub-types can be present simultaneously.
The following individual sub-types have been identified:
Cytotoxic In general, cytotoxic edema is linked to cell death in the brain through excessive cellular swelling. During cerebral ischemia for example, the blood–brain barrier remains intact but decreased blood flow and glucose supply leads to a disruption in cellular metabolism and creation of energy sources, such as adenosine triphosphate (ATP). Exhaustion of energy sources impairs functioning of the sodium and potassium pump in the cell membrane, leading to cellular retention of sodium ions. Accumulation of sodium in the cell causes a rapid uptake of water through osmosis, with subsequent swelling of the cells. The ultimate consequence of cytotoxic edema is the oncotic death of neurons. The swelling of the individual cells of the brain is the main distinguishing characteristic of cytotoxic edema, as opposed to vasogenic edema, wherein the influx of fluid is typically seen in the interstitial space rather than within the cells themselves. Researchers have proposed that "cellular edema" may be more preferable to the term "cytotoxic edema" given the distinct swelling and lack of consistent "toxic" substance involved.
There are several clinical conditions in which cytotoxic edema is present:
Commonly caused by traumatic brain injuries, intracerebral hemorrhage, and the early phase of ischemic stroke. Also seen in acute liver failure where toxic waste, most notably ammonia, accumulates in the blood stream and crosses the blood–brain barrier. Hyperammonemia in central nervous system (CNS) cells causes oxidative stress and mitochrondrial dysfunction, leading to astrocytic cell swelling. Additionally, ammonia is converted to glutamine in CNS cells which acts as an osmolyte and draws further water into the cell through osmosis. Cerebral edema occurs most commonly in conjunction with a rapid rise in ammonia levels. Toxic exposures to methionine sulfoximine, cuprizone, isoniazid, triethyltin, hexachlorophene, and hydrogen cyanide have been associated with cytotoxic edema and swelling of astrocytic cells. Hypoxia, anoxia can lead to cytotoxic edema through several mechanisms
Vasogenic Extracellular brain edema, or vasogenic edema, is caused by an increase in the permeability of the blood–brain barrier. The blood–brain barrier consists of astrocytes and pericytes joined with adhesion proteins producing tight junctions. Return of blood flow to these cells after an ischemic stroke can cause excitotoxicity and oxidative stress leading to dysfunction of the endothelial cells and disruption of the blood-brain barrier. The breakdown of the tight endothelial junctions that make up the blood–brain barrier causes extravasation of fluid, ions, and plasma proteins, such as albumin, into the brain parenchyma. Accumulation of extracellular fluid increases brain volume and then intracranial pressure causing the symptoms of cerebral edema.
There are several clinical conditions in which vasogenic edema is present:
CNS tumors, like glioblastoma and meningioma Infections like meningitis, abscess, and encephalitis Inflammatory central nervous system disease such as multiple sclerosis Brain hemorrhage Traumatic brain injuries can lead to increased intracranial pressure, local damage, reduced cerebral blood flow, and focal ischemia secondary to vasogenic edema. Late stage of ischemic stroke after rapid recovery from cytotoxic edema Hypertensive encephalopathy Radiation injury
Ionic (Osmotic) In ionic edema, the solute concentration (osmolality) of the brain exceeds that of the plasma and the abnormal pressure gradient leads to accumulation of water intake into the brain parenchyma through the process of osmosis. The blood-brain barrier is intact and maintains the osmotic gradient.
The solute concentration of the blood plasma can be diluted by several mechanisms:
Improper administration of intravenous fluids, isotonic or hypotonic. Excessive water intake, syndrome of inappropriate antidiuretic hormone (SIADH). Rapid reduction of blood glucose in diabetic ketoacidosis or hyperosmolar hyperglycemic state. Hemodialysis has been associated with ionic edema and cellular swelling. Cerebral edema is a potentially life-threatening complication of severely decreased sodium ion concentration in the blood (hyponatremia).
Ionic brain edema can also occur around the sites of brain hemorrhages, infarcts, or contusions due to a local plasma osmolality pressure gradient when compared to the high osmolality in the affected tissue.
Interstitial (hydrocephalic) Interstitial edema can be best characterized by a noncomunnicating hydrocephalus where there is an obstruction to the outflow of cerebrospinal fluid within the ventricular system. The obstruction creates a rise in the intraventricular pressure and causes CSF to flow through the wall of the ventricles into the extracellular fluid within brain. The fluid has roughly the same composition of CSF.
Other causes of interstitial edema include but are not limited to communicating hydrocephalus, and normal pressure hydrocephalus.
Hydrostatic Hydrostatic extracellular brain edema is typically caused by severe arterial hypertension. A difference in the hydrostatic pressure within the arterial system relative to the endothelial cells allows ultrafiltration of water, ions, and low molecular weight substances (such as glucose, small amino acids) into the brain parenchyma. The blood-brain barrier is intact usually and the extent of the edema depends on the arterial pressure. The regulatory processes of the brain circulation can function up to systolic arterial pressures of 150 mm Hg and will have impaired function at higher blood pressures.
Combined types of cerebral edema Cytotoxic, osmotic, and vasogenic edema exist on a continuum. The mechanism of the cause of cerebral edema can often overlap between these types. In most instances, cytotoxic and vasogenic edema occur together. When the two edema types evolve simultaneously, the damage of one type reaches a limit and will bring about the other type of injury. For example, when cytotoxic edema occurs in the endothelial cells of the blood–brain barrier, oncotic cell death contributes to loss of integrity of the blood–brain barrier and promotes the progression to vasogenic edema. When brain edema types are combined, there is typically a primary form and the edema type and context of the cause must be determined in order to start appropriate medical or surgical therapy. The use of specific MRI techniques has allowed for some differentiation between the mechanisms.
Subtypes
High-altitude cerebral edema If not properly acclimatized to high altitude, a person may be negatively affected by the lower oxygen concentration available. These hypoxia-related illnesses include acute mountain sickness (AMS), high-altitude pulmonary edema, and high-altitude cerebral edema (HACE). High-altitude cerebral edema is a severe and sometimes fatal form of altitude sickness that results from capillary fluid leakage due to the effects of hypoxia on the mitochondria-rich endothelial cells of the blood–brain barrier. The edema can be characterized by vasogenic cerebral edema with symptoms of impaired consciousness and truncal ataxia.